A proposal is presented to test and to define experimentally an immunoregulatory mechanism that is based upon a self-regulating network of antigen specific antibody-forming cell clones (clonotypes), and autologous idiotype specific antibody-forming cell clones (anti-clonotypes). After fusing immune spleen cells with a mutant myeloma cell line we are able to identify myeloma/spleen cell hybrids secreting monoclonal antibodies specific for the immunizing ligands (either a thymic independent, thymic dependent or tumor specific antigen) and myeloma/spleen cell hybrids secreting antibodies specific for autologous idiotypes on the antigen specific antibodies. By employing a rapid screening procedure with the cell fusing technique we can select, clone and cultivate hybrids secreting antigen-specific and idiotype specific antibodies from numerous immune spleen cell populations. The ability of some resultant hybrids to secrete idiotype specific antibodies presumably reflects the generation of idiotype reactive cells under physiological conditions which is consistent with the proposed network theory. With large quantities of purified idiotype specific and antigen specific antibodies which result from the hybrids we will define selected clonal products in terms of their isotype, specificity, banding patterns in isoelectric focusing, and amino acid sequences. Having characterized the anti-idiotype antibodies immunochemically we will determine the effect (enhancing or inhibiting) of the passive transfer of the anti-idiotypes following immunization. We shall determine whether there is a correlation between the immunochemical nature of the anti-idiotype antibodies and their ability to enhance or suppress expression of individual clonotypes. By selective exposure of B cells and T cells to anti-idiotype antibodies we shall determine the target of the autologous anti-idiotype induced effect and whether this effect is mediated directly by antibody or indirectly via generation of idiotype reactive helper or suppressor cells.